INFLUX OF NEUTROPHILS INTO THE WALLS OF LARGE EPICARDIAL CORONARY-ARTERIES IN RESPONSE TO ISCHEMIA REPERFUSION
INFLUX OF NEUTROPHILS INTO THE WALLS OF LARGE EPICARDIAL CORONARY-ARTERIES IN RESPONSE TO ISCHEMIA REPERFUSION
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DOI：
10.1161/01.cir.84.4.1758
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发表时间：
1991-10-01
期刊：
影响因子：
37.8
通讯作者：
BELLOWS, S
中科院分区：
文献类型：
--
作者：
KLONER, RA;GIACOMELLI, F;BELLOWS, S
背景 存在几种临床情况，其中大的心外膜冠状动脉被剥夺了血流，例如当阻塞性血栓或栓子停留在血管内或在冠状动脉夹层期间时发生。 关于血流剥夺对大的心外膜冠状动脉的影响的信息很少。 我们研究了一个模型，在该模型中，一段大的心外膜冠状动脉被剥夺了血流，使用近端和远端钳3小时，然后再灌注。 通过动脉横截面的光学显微镜检查，在缺血/再灌注血管的内膜中存在19 +/-6个中性粒细胞，而在非缺血血管的内膜中仅存在平均4 +/-3（SEM）个中性粒细胞（p < 0.02）。 平均而言，在缺血/再灌注血管的弹性膜下有17 +/- 9个中性粒细胞，而在非缺血血管中无中性粒细胞（p < 0.05）;在缺血/再灌注血管的中膜内有16 +/- 10个中性粒细胞，而在非缺血血管中无中性粒细胞（p < 0.05）。 电子显微镜分析显示，中性粒细胞在缺血/再灌注血管往往是“夹”之间的内皮细胞和弹性膜。 心肌内的超微结构异常还显示微血管损伤，包括血管内存在中性粒细胞和红细胞淤滞。 为了排除心外膜大动脉中的发现是由于隔离动脉段内静态血液中的有毒物质所致的可能性，执行了一项方案，其中从隔离动脉段中取出血液。 再次观察到中性粒细胞浸润到血管中。 冠状动脉闭塞前静息平均心外膜冠状动脉血流量为19 +/- 3 ml/min;再灌注后2.5小时的平均冠状动脉血流量相同，为19 +/- 3 ml/min。（乙酰胆碱）和内皮非依赖性血管舒张（硝酸甘油）激发在再灌注后早期是正常的，但在再灌注后晚期被抑制，提示在该模型中进行性血管功能障碍，因此是血管再灌注损伤的一种形式。在该模型中，当大的心外膜冠状动脉被剥夺血流，然后再灌注时，嗜中性粒细胞迁移到血管壁以及微脉管系统中。 这些异常与内皮依赖性和内皮非依赖性冠状动脉血管舒张功能储备降低有关。
Background. There are several clinical situations in which large epicardial coronary arteries are deprived of blood flow, such as occurs when an obstructing thrombus or embolus lodges within a vessel or during coronary dissection. There is little information concerning the effect of flow deprivation on large epicardial coronary arteries.Methods and Results. We studied a model in which a segment of a large epicardial coronary artery was deprived of blood flow using both proximal and distal clamps for 3 hours followed by reperfusion. On examination by light microscopy of cross sections of the arteries, 19 +/- 6 neutrophils were present in the intima of ischemic/reperfused vessels, whereas only a mean of 4 +/- 3 (SEM) were present in the intima of nonischemic vessels (p < 0.02). On average, there were 17 +/- 9 neutrophils just under the elastic lamina in ischemic/reperfused vessels versus none in the nonischemic vessels (p < 0.05); there were 16 +/- 10 neutrophils present within the media of ischemic/reperfused vessels, and none (p < 0.05) in the nonishemic vessels. Electron microscopic analysis revealed that neutrophils in the ischemic/reperfused vessels were often "sandwiched" between the endothelial cells and the elastic lamina. Ultrastructural abnormalities within the myocardium also revealed damage to the microvasculature, including the presence of neutrophils within the vessels and erythrocyte stasis. To rule out the possibility that findings in the large epicardial arteries were due to toxic substances from static blood within the isolated arterial segment, a protocol was performed in which blood was removed from the isolated segment. Again, neutrophil infiltration into the vessel was observed. Resting mean epicardial coronary artery blood flow before coronary occlusion was 19 +/- 3 ml/min; mean coronary blood flow 2.5 hours after reperfusion was identical at 19 +/- 3 ml/min. Response to both endothelial-dependent vasodilation (acetylcholine) and endothelial-independent vasodilation (nitroglycerin) challenges was normal early after reperfusion but was depressed late after reperfusion, suggesting progressive vascular dysfunction and hence a form of vascular reperfusion injury in this model.Conclusions: When large epicardial coronary arteries are deprived of blood flow, followed by reperfusion in this model, neutrophils migrate into the vessel wall as well as into the microvasculature. These abnormalities are associated with reduced endothelial-dependent and endothelial-independent coronary vasodilator reserve.